Lisa H Shiue1,2, Jacob Couturier3,4, Dorothy E Lewis3,4, Caimiao Wei5, Xiao Ni1,2, Madeleine Duvic1,2. 1. Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 2. Graduate Program in Immunology, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA. 3. Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA. 4. Graduate Program in Virology, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA. 5. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Abstract
PURPOSE: Extracorporeal photopheresis (ECP) alone or in combination therapy is effective for treatment of leukemic cutaneous T-cell lymphoma (L-CTCL), but its mechanism(s) of action remain unclear. This study was designed to investigate the effect of ECP on regulatory T cells and CD8(+) T cells in L-CTCL patients. EXPERIMENTAL DESIGN: Peripheral blood from 18 L-CTCL patients at baseline, Day 2, 1 month, 3 month, and 6 month post-ECP therapy was analyzed by flow cytometry for CD4(+) CD25(+/high) , CD4(+) Foxp3(+) CD25(+/-) , CD3(+) CD8(+) , CD3(+) CD8(+) CD69(+) , and CD3(+) CD8(+) IFN-γ(+) T cells. Clinical responses were assessed and correlated with changes in these T-cell subsets. RESULTS: Twelve of 18 patients achieved clinical responses. The average baseline number of CD4(+) CD25(+/high) T cells of PBMCs in L-CTCL patients was normal (2.2%), but increased at 6-month post-therapy (4.3%, P < 0.01). The average baseline number of CD4(+) Foxp3(+) T cells out of CD4(+) T cells in nine evaluable patients was high (66.8 ± 13.7%), mostly CD25 negative. The levels of CD4(+) Foxp3(+) T cells in responders were higher (n = 6, 93.1 ± 5.7%) than nonresponders (n = 3, 14.2 ± 16.0%, P < 0.01), and they declined in parallel with malignant T cells. The numbers of CD3(+) CD8(+) CD69(+) and CD3(+) CD8(+) IFN-γ(+) T cells increased at 3-month post-therapy in five of six patients studied. CONCLUSIONS: Extracorporeal photopheresis alone or in combination therapy might be effective in L-CTCL patients whose malignant T cells have a CD4(+) Foxp3(+) CD25(-) phenotype.
PURPOSE: Extracorporeal photopheresis (ECP) alone or in combination therapy is effective for treatment of leukemic cutaneous T-cell lymphoma (L-CTCL), but its mechanism(s) of action remain unclear. This study was designed to investigate the effect of ECP on regulatory T cells and CD8(+) T cells in L-CTCLpatients. EXPERIMENTAL DESIGN: Peripheral blood from 18 L-CTCLpatients at baseline, Day 2, 1 month, 3 month, and 6 month post-ECP therapy was analyzed by flow cytometry for CD4(+) CD25(+/high) , CD4(+) Foxp3(+) CD25(+/-) , CD3(+) CD8(+) , CD3(+) CD8(+) CD69(+) , and CD3(+) CD8(+) IFN-γ(+) T cells. Clinical responses were assessed and correlated with changes in these T-cell subsets. RESULTS: Twelve of 18 patients achieved clinical responses. The average baseline number of CD4(+) CD25(+/high) T cells of PBMCs in L-CTCLpatients was normal (2.2%), but increased at 6-month post-therapy (4.3%, P < 0.01). The average baseline number of CD4(+) Foxp3(+) T cells out of CD4(+) T cells in nine evaluable patients was high (66.8 ± 13.7%), mostly CD25 negative. The levels of CD4(+) Foxp3(+) T cells in responders were higher (n = 6, 93.1 ± 5.7%) than nonresponders (n = 3, 14.2 ± 16.0%, P < 0.01), and they declined in parallel with malignant T cells. The numbers of CD3(+) CD8(+) CD69(+) and CD3(+) CD8(+) IFN-γ(+) T cells increased at 3-month post-therapy in five of six patients studied. CONCLUSIONS: Extracorporeal photopheresis alone or in combination therapy might be effective in L-CTCLpatients whose malignant T cells have a CD4(+) Foxp3(+) CD25(-) phenotype.
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